The present invention relates to a process for producing an organotitanium compound useful for production of pharmaceuticals and agricultural chemicals and their intermediates and also to a process for addition reaction involving the organotitanium compound. More particularly, the present invention relates to a process for producing an organotitanium compound useful for production of polysubstituted benzene or polysubstituted pyridine.
There is an established process known as Reppe reaction for producing a benzene compound directly from three acetylene compounds in the presence of a catalyst of transition metal catalyst. This reaction, however, has difficulty in producing a polysubstituted benzene compound regioselectively from substituted acetylene compounds.
As for regioselective production of a substituted benzene compound from three acetylene compounds, several processes are disclosed in Chem. Rev. 2000, 100, 2901-2915. These processes are based on condensation of one molecule of diyne compound and one molecule of acetylene compound. Nothing is mentioned about the process of producing a substituted benzene compound regioselectively from three molecules of acetylene compound.
There is known a process for producing a pyridine compound regioselectively from two acetylene compounds and one nitrile compound. (J. Chem. Soc., Dalton 1978, 1278-1282, J. Am. Chem. Soc. 2000, 122, 4994-4995)
The process disclosed in the former literature has the disadvantage of requiring an expensive cobalt complex and being incapable of using two acetylene compounds of different kind. The process disclosed in the latter literature has the disadvantage of requiring an expensive zirconium catalyst and also requiring two-stage reactions with different catalysts. Therefore, both processes are not suitable for industrial production.
The present invention was completed in view of the foregoing. Accordingly, it is an object of the present invention to provide a process for producing an organotitanium compound capable of regioselectively converting a substituted acetylene compound into a polysubstituted benzene compound or a polysubstituted pyridine compound. It is another object of the present invention to provide a process for addition reaction to produce polysubstituted benzene and polysubstituted pyridine through addition of an electrophilic reagent to the organotitanium compound.
In order to achieve the above-mentioned object, the present inventors carried out extensive studies, which led to the finding that it is possible to produce an organotitanium compound from a titanium reagent as a reaction product of a tetravalent titanium compound (which is commercially inexpensive) and a Grignard reagent, the organotitanium compound being capable of converting three molecules of acetylene compound, or one molecule of acetylene compound and one molecule of diyne compound, into a benzene compound regioselectively, or converting two molecules of acetylene compound and one molecule of nitrile compound into a pyridine compound regioselectively. The present invention is based on this finding.
The present invention provides the following.
[1] A process for producing an organotitanium compound which comprises reacting an acetylene compound represented by the formula (1) below in the presence of a titanium compound represented by the formula (2) below and a Grignard reagent represented by the formula (3) below with an acetylene compound represented by the formula (4) below and further reacting with a compound represented by the formula (5) below, thereby giving the titanium compound represented by the formula (6) and/or (7) below. 
[where R1 and R2 denote mutually independently a C1-20 alkyl group {which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 denote mutually independently a C1-6 alkyl group or phenyl group)}, C3-20 alkenyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, di-C1-6-alkylaminocarbonyl group, phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, or di-C1-6-alkylaminocarbonyl group), furyl group, amino group, SiR7R8R9 (where R7, R8, and R9 denote mutually independently a C1-6 alkyl group or phenyl group), or SnR10R11R12 (where R10, R11, and R12 denote mutually independently a halogen atom, C1-6 alkyl group, or phenyl group).]
TiX1X2X3X4xe2x80x83xe2x80x83(2)
[where X1, X2, X3, and X4 denote mutually independently a halogen atom, C1-6 alkoxy group {which may be substituted with a phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group) or naphthyl group}, phenoxy group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenoxy group), or naphthoxy group.]
RMgX5xe2x80x83xe2x80x83(3)
[where R denotes a C2-8 alkyl group having a hydrogen atom at the xcex2 position, and X5 denotes a halogen atom.]
[where R3 and R4 denote mutually independently a hydrogen atom, C1-20 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, di-C1-6-alkylamino-carbonyl group, phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, or di-C1-6-alkylaminocarbonyl group), furyl group, amino group, SiR7R8R9 (where R7, R8, and R9 are defined as above), or SnR10R11R12 (where R10, R11, and R12 are defined as above).]
[where R5 denotes a hydrogen atom, C1-20 alkyl group, or phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, or di-C1-6-alkylaminocarbonyl group); Z denotes CRxe2x80x2 (where Rxe2x80x2 denotes a hydrogen atom or C1-20 alkyl group) or a nitrogen atom; X6 denotes a halogen atom, C1-6 alkoxy group {which may be substituted with a phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group) or naphthyl group}, phenoxy group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), naphthoxy group, SOnR6 group {where R6 denotes a C1-6 alkyl group or phenyl group (which may be substituted with a halogen atom or C1-6 alkyl group) and n denotes 1 or 2}, OSO2R6 group (where R6 is defined as above), or OP(O)(OR13)2 group (where R13 denotes a C1-6 alkyl group); and m denotes 0 or 1.]
[where R1xcx9cR5, Z, X6, and m are defined as above; and Xp and Xq denote any of X1xcx9cX4 (which are defined as above).]
[2] A process for producing an organotitanium compound which comprises reacting an acetylene compound represented by the formula (8) below in the presence of a titanium compound represented by the formula (2) below and a Grignard reagent represented by the formula (3) below with a compound represented by the formula (5) below, thereby giving the titanium compound represented by the formula (9) and/or (10) below. 
[where R1 denotes a C1-20 alkyl group {which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 denote mutually independently a C1-6 alkyl group or phenyl group)}, C3-20 alkenyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, di-C1-6-alkyaminocarbonyl group, phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, or di-C1-6-alkylaminocarbonyl group), furyl group, amino group, SiR7R8R9 (where R7, R8, and R9 are defined as above), or SnR10R11R12 (where R10, R11, and R12 denote mutually independently a halogen atom, C1-6 alkyl group, or phenyl group); R4 denotes a hydrogen atom, C1-20 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylamino-carbonyl group, di-C1-6-alkylaminocarbonyl group, phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylamino-carbonyl group, or di-C1-6-alkylaminocarbonyl group), furyl group, amino group, SiR7R8R9 (where R7, R8, and R9 are defined as above), or SnR10R11R12 (where R10, R11, and R12 are defined as above); and Y denotes Z1-Z2-Z3 or Z4-Z5-Z6-Z7 (where Z1, Z3, Z4, Z5, and Z7 denote mutually independently Cxe2x95x90O or CR14R15  less than where R14 and R15 denote mutually independently a hydrogen atom or C1-6 alkyl group (which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 are defined as above)) greater than , Z2 and Z6 denote mutually independently O, S, Cxe2x95x90O, NR16  less than where R16 denotes a C1-6 alkyl group (which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 are defined as above)) greater than , or CR14xe2x80x2R15xe2x80x2  less than where R14xe2x80x2 and R15xe2x80x2 denote mutually independently a hydrogen atom or C1-6 alkyl group (which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 are defined as above)) greater than }.]
TiX1X2X3X4xe2x80x83xe2x80x83(2)
[where X1, X2, X3, and X4 denote mutually independently a halogen atom, C1-6 alkoxy group {which may be substituted with a phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), or a naphthyl group)}, phenoxy group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), or naphthoxy group.]
RMgX5xe2x80x83xe2x80x83(3)
[where R denotes a C2-8 alkyl group having a hydrogen atom at the xcex2 position, and X5 denotes a halogen atom.]
[where R5 denotes a hydrogen atom, C1-20 alkyl group, or phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, or di-C1-6-alkylaminocarbonyl group), Z denotes CRxe2x80x2 (where Rxe2x80x2 denotes a hydrogen atom or C1-20 alkyl group) or a nitrogen atom; X6 denotes a halogen atom, C1-6 alkoxy group {which may be substituted with a phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), or naphthyl group}, phenoxy group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), naphthoxy group, SOnR6 {where R6 denotes a C1-6 alkyl group or phenyl group (which may be substituted with a halogen atom or C1-6 alkyl group) and n denotes 1 or 2}, OSO2R6 (where R6 is defined as above), or OP(O)(OR13)2 group (where R13 denotes a C1-6 alkyl group); and m denotes 0 or 1.]
[where R1, R4, R5, Y, Z, X6, and m are defined as above; and Xp and Xq denote any of X1xcx9cX4 (which are defined as above).]
[3] A process for producing an organotitanium compound which comprises reacting an acetylene compound represented by the formula (1) below in the presence of a titanium compound represented by the formula (2) below and a Grignard reagent represented by the formula (3) below with a compound represented by the formula (11) below, thereby giving the titanium compound represented by the formula (12) below. 
[where R1 and R2 denote mutually independently a C1-20 alkyl group {which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 denote mutually independently a C1-6 alkyl group or phenyl group)}, C3-20 alkenyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, di-C1-6-alkyaminocarbonyl group, phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6-alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, or di-C1-6-alkylaminocarbonyl group), furyl group, amino group, SiR7R8R9 (where R7, R8, and R9 are defined as above), or SnR10R11R 12 (where R10, R11, and R12 denote mutually independently a halogen atom, C1-6 alkyl group, or phenyl group).]
TiX1X2X3X4xe2x80x83xe2x80x83(2)
[where X1, X2, X3, and X4 denote mutually independently a halogen atom, C1-6 alkoxy group {which may be substituted with a phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), or a naphthyl group}, phenoxy group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), or naphthoxy group).]
RMgX5xe2x80x83xe2x80x83(3)
[where R denotes a C2-8 alkyl group having a hydrogen atom at the xcex2 position, and X5 denotes a halogen atom.]
[where R3 denotes a hydrogen atom, C1-20 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylamino-carbonyl group, di-C1-6-alkylaminocarbonyl group, phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylamino-carbonyl group, or di-C1-6-alkylaminocarbonyl group), furyl group, amino group, SiR7R8R9 (R7, R8, and R9 are defined as above), or SnR10R11R12 (where R10, R11, and R12 are defined as above); R5 denotes a hydrogen atom, C1-20 alkyl group, or phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, or di-C1-6-alkylaminocarbonyl group); Yxe2x80x2 denotes Z1-Z2-Z3 or Z4-Z5-Z6-Z7 {where Z1, Z3, Z4, Z5, and Z7 denote mutually independently Cxe2x95x90O or CR14R15  less than where R14 and R15 denote mutually independently a hydrogen atom or C1-6 alkyl group (which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 are defined as above)) greater than , Z2 and Z6 denote mutually independently O, S, Cxe2x95x90O, NR16 (where R16 denotes a C1-6 alkyl group (which may be substituted with C1-6 alkoxy group (which may be substituted with a phenyl group)) or OSiR7R8R9 (where R7, R8, and R9 are defined as above) greater than , or CR14xe2x80x2R15xe2x80x2  less than where R14xe2x80x2 and R15xe2x80x2 denote mutually independently a hydrogen atom, C1-6 alkyl group (which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 are defined as above)) greater than }; X6 denotes a halogen atom, C1-6 alkoxy group {which may be substituted with a phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), or naphthyl group), phenoxy group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), naphthoxy group, SOnR6 {where R6 denotes a C1-6 alkyl group or phenyl group (which may be substituted with a halogen atom or C1-6 alkyl group), and n denotes 1 or 2}, OSO2R6 (where R6 is defined as above), or OP(O)(OR13)2 group (where R13 denotes a C1-6 alkyl group); and m denotes 0 or 1.]
[where R1 to R3, R5, Yxe2x80x2, X6, and m are defined as above; and Xp and Xq denote any of X1xcx9cX4 (which are defined as above).]
[4] A process for producing an organotitanium compound which comprises reacting an acetylene compound represented by the formula (1) below in the presence of a titanium compound represented by the formula (2) below and a Grignard reagent represented by the formula (3) below with a compound represented by the formula (13) below, thereby giving the titanium compound represented by the formula (14) below. 
[where R1 and R2 denote mutually independently a C1-20 alkyl group {which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 denote mutually independently a C1-6 alkyl group or phenyl group)}, C3-20 alkenyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, di-C1-6-alkyaminocarbonyl group, phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, or di-C1-6-alkylaminocarbonyl group), furyl group, amino group, SiR7R8R9 (where R7, R8, and R9 denote mutually independently a C1-6 alkyl group or phenyl group), or SnR10R11R12 (where R10, R11, and R12 denote mutually independently a halogen atom, C1-6 alkyl group, or phenyl group).]
TiX1X2X3X4xe2x80x83xe2x80x83(2)
[where X1, X2, X3, and X4 denote mutually independently a halogen atom, C1-6 alkoxy group {which may be substituted with a phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group) or naphthyl group}, phenoxy group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), or naphthoxy group.]
RMgX5xe2x80x83xe2x80x83(3)
[where R denotes a C2-8 alkyl group having a hydrogen atom at the xcex2 position, and X5 denotes a halogen atom.]
[where Rxe2x80x2 denotes a hydrogen atom or C1-20 alkyl group; and X6 denotes a halogen atom, C1-6 alkoxy group (which may be substituted with a phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group) or naphthyl group}, phenoxy group (which may be substituted with C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), naphthoxy group, SOnR6 group {where R6 denotes a C1-6 alkyl group or phenyl group (which may be substituted with a halogen atom or C1-6 alkyl group), and n denotes 1 or 2}, OSO2R6 (where R6 is defined as above), or OP(O)(OR13)2 group (where R13 denotes a C1-6 alkyl group).]
[where R1, R2, Rxe2x80x2, Z, and X6 are defined as above; and Xp and Xq denote any of X1 to X4 (which are defined as above).]
[5] A process for producing an organotitanium compound as defined in any of [1] to [4] above, wherein the titanium compound is tetra-i-propoxytitanium.
[6] A process for producing an organotitanium compound as defined in any of [1] to [5] above, wherein the Grignard reagent is an i-propyl Grignard reagent.
[7] A process for addition reaction which comprises adding to the organotitanium compound obtained by the process defined in any of [1] to [6] above a compound having an electrophilic functional group or an electrophilic reagent, and performing addition reaction on the organotitanium compound.
[8] A process for addition reaction as defined in [7] above, wherein the electrophilic functional group is an aldehyde group, ketone group, imino group, hydrazone group, aliphatic double bond, aliphatic triple bond, acyl group, ester group, or carbonate group.
[9] A process for addition reaction as defined in [7] above, wherein the electrophilic reagent is water, heavy water, chlorine, bromine, iodine, N-bromosuccinimide, oxygen, carbon dioxide gas, or carbon monoxide.
The invention will be described in more detail in the following. Incidentally, throughout this specification, xe2x80x9cnxe2x80x9d implies xe2x80x9cnormalxe2x80x9d, xe2x80x9cixe2x80x9d implies xe2x80x9cisoxe2x80x9d, xe2x80x9csxe2x80x9d implies xe2x80x9csecondaryxe2x80x9d, xe2x80x9ctxe2x80x9d implies xe2x80x9ctertiaryxe2x80x9d, xe2x80x9ccxe2x80x9d implies xe2x80x9ccycloxe2x80x9d, xe2x80x9coxe2x80x9d implies xe2x80x9corthoxe2x80x9d, xe2x80x9cmxe2x80x9d implies xe2x80x9cmetaxe2x80x9d, and xe2x80x9cpxe2x80x9d implies xe2x80x9cparaxe2x80x9d.
(A) Process for Producing Organotitanium Compound
In the acetylene compound represented by the formula (1), R1 and R2 denote mutually independently a C1-20 alkyl group {which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 denote mutually independently a C1-6 alkyl group or phenyl group)}, C3-20 alkenyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, di-C1-6-alkyaminocarbonyl group, phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, or di-C1-6-alkylaminocarbonyl group), furyl group, amino group, SiR7R8R9 (where R7, R8, and R9 denote mutually independently a C1-6 alkyl group or phenyl group), or SnR10R11R12 (where R10, R11, and R12 denote mutually independently a halogen atom, C1-6 alkyl group, or phenyl group).
The C1-20 alkyl group may be a straight, branched, or cyclic one. It includes, for example, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, c-pentyl, n-hexyl, c-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, n-nonadecyl, and eicosanyl. It also includes those substituted alkyl groups, such as 2-methoxyethyl, 2-ethoxyethyl, 2-benzyloxyethyl, 2-trimethylsiloxyethyl, 2-t-butyldimethylsiloxyethyl, 2-t-butyldiphenylsiloxyethyl, 3-methoxypropyl, 3-ethoxypropyl, 3-benzyloxypropyl, 3-trimethylsiloxypropyl, 3-t-butyldimethylsiloxypropyl, 3-t-butyldiephenylsiloxypropyl, 4-methoxybutyl, 4-ethoxybutyl, 4-benzyloxybutyl, 4-trimethylsiloxybutyl, 4-t-butyldimethylsiloxybutyl, and 4-t-butyldiphenylsiloxybutyl.
Of these examples, favorable ones are methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, 2-methoxyethyl, 2-ethoxyethyl, 2-benzyloxyethyl, 2-trimethylsiloxyethyl, 2-t-butylmethylsiloxyethyl, and 2-t-butyldiphenylsiloxyethyl. Particularly favorable ones are methyl, n-butyl, n-hexyl, 2-bentyloxyethyl, and 2-t-butyldimethylsiloxyethyl.
The C3-20 alkenyl group may be a straight, branched, or cyclic one. It includes, for example, allyl, 2-butenyl, 3-butenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 6-heptenyl, 7-octenyl, 3,7-dimethyl-6-octenyl, 8-nonenyl, 9-decenyl, 10-undecenyl, 11-dodecenyl, 12-tridecenyl, 13-tetradecenyl, 14-pentadecenyl, 15-hexadecenyl, 16-heptadecenyl, 17-octadecenyl, 18-nonadecenyl, and 19-eicosenyl. Of these examples, 3,7-dimethyl-6-octenyl is favorable.
The C1-6 alkoxy group may be a straight, branched, or cyclic one. It includes, for example, methoxy, ethoxy, n-propoxy, i-propoxy, c-propoxy, n-butoxy, i-butoxy, s-butoxy, t-butoxy, c-butoxy, 1-methyl-c-propoxy, 2-methyl-c-propoxy, pentoxy, c-pentoxy, hexoxy, and c-hexoxy. Of these examples, favorable ones are methoxy, ethoxy, n-butoxy, c-pentoxy, n-hexoxy, and c-hexoxy. c-Hexoxy is particularly favorable.
The C1-6 alkoxycarbonyl group is not specifically restricted so long as it is a carbonyl group having the above-mentioned C1-6 alkoxy group. It includes, for example, methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, i-propoxycarbonyl, n-butoxycarbonyl, i-butoxycarbonyl, t-butoxycarbonyl, t-amyloxycarbonyl, vinyloxycarbonyl, allyloxycarbonyl, 2-(trimethylsilyl)ethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, pentoxycarbonyl, and hexoxycarbonyl. Of these examples, favorable ones are methoxycarbonyl, ethoxycarbonyl, n-butoxycarbonyl, and t-butoxycarbonyl, and particularly favorable ones are ethoxycarbonyl and t-butoxycarbonyl.
The C1-6 alkyl group may be a straight, branched, or cyclic one. It includes, for example, methyl, ethyl, n-propyl, i-propyl, c-propyl, n-butyl, i-butyl, s-butyl, t-butyl, c-butyl, 1-methyl-c-propyl, 2-methyl-c-propyl, n-pentyl, 1-methyl-n-butyl, 2-methyl-n-butyl, 3-methyl-n-butyl, 1,1-dimethyl-n-propyl, 1,2-dimethyl-n-propyl, 2,2-dimethyl-n-propyl, 1-ethyl-n-propyl, c-pentyl, 1-methyl-c-butyl, 2-methyl-c-butyl, 3-methyl-c-butyl, 1,2-dimethyl-c-propyl, 2,3-dimethyl-c-propyl, 1-ethyl-c-propyl, 2-ethyl-c-propyl, n-hexyl, 1-methyl-n-pentyl, 2-methyl-n-pentyl, 3-methyl-n-pentyl, 4-methyl-n-pentyl, 1,1-dimethyl-n-butyl, 1,2-dimethyl-n-butyl, 1,3-dimethyl-n-butyl, 2,2-dimethyl-n-butyl, 2,3-dimethyl-n-butyl, 3,3-dimethyl-n-butyl, 1-ethyl-n-butyl, 2-ethyl-n-butyl, 1,1,2-trimethyl-n-propyl, 1,2,2-trimethyl-n-propyl, 1-ethyl-1-methyl-n-propyl, 1-ethyl-2-methyl-n-propyl, c-hexyl, 1-methyl-c-pentyl, 2-methyl-c-pentyl, 3-methyl-c-pentyl, 1-ethyl-c-butyl, 2-ethyl-c-butyl, 3-ethyl-c-butyl, 1,2-dimethyl-c-butyl, 1,3-dimethy-c-butyl, 2,2-dimethyl-c-butyl, 2,3-dimethyl-c-butyl, 2,4-dimethyl-c-butyl, 3,3-dimethyl-c-butyl, 1-n-propyl-c-propyl, 2-n-propyl-c-propyl, 1-i-propyl-c-propyl, 2-i-propyl-c-propyl, 1,2,2-trimethyl-c-propyl, 1,2,3-trimethyl-c-propyl, 2,2,3-trimethyl-c-propyl, 1-ethyl-2-methyl-c-propyl, 2-ethyl-1-methyl-c-propyl, 2-ethyl-2-methyl-c-propyl, and 2-ethyl-3-methyl-c-propyl.
The C1-6 alkylaminocarbonyl group and di-C1-6-alkyl-aminocarbonyl group are not specifically restricted so long as they are (di)alkylaminocarbonyl groups having the above-mentioned C1-6 alkyl group on the nitrogen atom. They include, for example, (di)methylaminocarbonyl, (di)ethylaminocarbonyl, (di)propylaminocarbonyl, and (di)butylaminocarbonyl. Of these examples, favorable ones are (di)methylaminocarbonyl, (di)ethylaminocarbonyl, and (di)n-propylaminocarbonyl. Particularly favorable one is (di)ethylaminocarbonyl.
The phenyl group includes, for example, phenyl, o-methylphenyl, m-methylphenyl, p-methylphenyl, p-ethylphenyl, p-i-propylphenyl, p-t-butylphenyl, o-methoxyphenyl, p-methoxyphenyl, 3,5-dimethylphenyl, 3,5-dimethoxyphenyl, 3,5-diethylphenyl, 3,5-di-i-propylphenyl, 2,4,6-trimethylphenyl, and 2,4,6-trimethoxyphenyl. Of these examples, phenyl is favorable.
The SiR7R8R9 group is not specifically restricted so long as its substituent groups (any of R7, R8, and R9) are mutually independently a C1-6 alkyl group or phenyl group. It includes, for example, trimethylsilyl, triethylsilyl, triisopropylsilyl, tributylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, diphenylmethylsilyl, and triphenyl-silyl. Of these examples, favorable ones are trimethylsilyl, t-butyldimethylsilyl, and t-butyldiphenylsilyl. Particularly favorable ones are trimethylsilyl and t-butyldimethylsilyl.
The SnR10R11R12 group is not specifically restricted so long as its substituent groups (any of R10, R11, and R12) are mutually independently a halogen atom, C1-6 alkyl group, or phenyl group. It includes, for example, trimethyltin, triethyltin, tributyltin, trichlorotin, and triphenyltin. Of these examples, favorable ones are trimethyltin, triphenyltin, and trichlorotin.
Incidentally, the halogen atom may be any of fluorine, chlorine, bromine, and iodine.
In the titanium compound represented by the formula (2) above, X1, X2, X3, and X4 denote mutually independently a halogen atom, C1-6 alkoxy group {which may be substituted with a phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group) or naphthyl group}, phenoxy group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenoxy group), or naphthoxy group.
The C1-6 alkoxy group includes (in addition to the above-exemplified alkoxy groups) benzyloxy, o-methylbenzyloxy, m-methylbenzyloxy, p-methylbenzyloxy, o-methoxybenzyloxy, p-methoxybenzyloxy, phenethyloxy, o-methylphenethyloxy, m-methylphenethyloxy, p-methylphenethyloxy, o-methoxyphenethyloxy, p-methoxyphenethyloxy, 3-pheylpropoxy, 4-phenylbutoxy, 5-phenylpentoxy, 6-phenylhexoxy, xcex1-naphthylmethoxy, xcex2-naphthylmethoxy, o-biphenylylmethoxy, m-biphenylylmethoxy, p-biphenylylmethoxy, xcex1-naphthylethoxy, xcex2-naphthylethoxy, o-biphenylylethoxy, m-biphenylylethoxy, and p-biphenylylethoxy. Of these examples, favorable ones are methoxy, ethoxy, n-propoxy, i-propoxy, and n-butoxy.
The phenoxy group or naphthoxy group is not specifically restricted; it includes, for example, phenoxy, o-methylphenoxy, m-methylphenoxy, p-methylphenoxy, p-ethylphenoxy, p-i-propylphenoxy, p-t-butylphenoxy, o-methoxyphenoxy, p-methoxyphenoxy, xcex1-naphthoxy, xcex2-naphthoxy, o-biphenyloxy, m-biphenyloxy, and p-biphenyloxy.
The halogen atom X is not specifically restricted as mentioned above. A favorable halogen is chlorine.
Incidentally, the C1-6 alkyl group is defined as above.
Typical examples of the titanium compound include tetra-i-propoxytitanium, chlorotri-i-propoxytitanium, and dichlorodi-i-propoxytitanium. Of these examples, tetra-i-propoxytitanium is favorable.
In the Grignard reagent represented by the formula (3) above, R denotes a C2-8 alkyl group having a hydrogen atom at the xcex2 position, and X5 denotes a halogen atom.
R (which is a C2-8 alkyl group having a hydrogen atom at the xcex2 position) may be a straight, branched, or cyclic alkyl group which is not specifically restricted so long as it has a hydrogen atom at the xcex2 position. It includes, for example, ethyl, n-propyl, i-propyl, c-propyl, n-butyl, i-butyl, s-butyl, t-butyl, c-butyl, 1-methyl-c-propyl, 2-methyl-c-propyl, n-pentyl, 1-methyl-n-butyl, 2-methyl-n-butyl, 3-methyl-n-butyl, 1,1-dimethyl-n-propyl, 1,2-dimethyl-n-propyl, 1-ethyl-n-propyl, c-pentyl, 1-methyl-c-butyl, 2-methyl-c-butyl, 3-methyl-c-butyl, 1,2-dimethyl-c-propyl, 2,3-dimethyl-c-propyl, 1-ethyl-c-propyl, 2-ethyl-c-propyl, n-hexyl, 1-methyl-n-pentyl, 2-methyl-n-pentyl, 3-methyl-n-pentyl, 4-methyl-n-pentyl, 1,1-dimethyl-n-butyl, 1,2-dimethyl-n-butyl, 1,3-dimethyl-n-butyl, 2,3-dimethyl-n-butyl, 3,3-diemthyl-n-butyl, 1-ethyl-n-butyl, 2-ethyl-n-butyl, 1,1,2-trimethyl-n-propyl, 1-ethyl-1-methyl-n-propyl, 1-ethyl-2-methyl-n-propyl, c-hexyl, 1-methyl-c-pentyl, 2-methyl-c-pentyl, 3-methyl-c-pentyl, 1-ethyl-c-butyl, 2-ethyl-c-butyl, 3-ethyl-c-butyl, 1,2-dimethyl-c-butyl, 1,3-dimethyl-c-butyl, 2,2-dimethyl-c-butyl, 2,3-dimethyl-c-butyl, 2,4-dimethyl-c-butyl, 3,3-dimethyl-c-butyl, 1-n-propyl-c-propyl, 2-n-propyl-c-propyl, 1-i-propyl-c-propyl, 2-i-propyl-c-propyl, 1,2,2-trimethyl-c-propyl, 1,2,3-trimethyl-c-propyl, 2,2,3-trimethyl-c-propyl, 1-ethyl-2-methyl-c-propyl, 2-ethyl-1-methyl-c-propyl, 2-ethyl-2-methyl-c-propyl, 2-ethyl-3-methyl-c-propyl, n-heptyl, 5-methyl-n-hexyl, c-heptyl, n-octyl, 6-methyl-n-heptyl, and c-octyl. Of these examples, favorable ones are ethyl, n-propyl, i-propyl, n-butyl, and i-butyl.
The halogen atom (X5) is not specifically restricted. Favorable ones are chlorine and bromine.
Typical examples of the Grignard reagent include ethyl Grignard reagent (such as ethyl magnesium chloride and ethyl magnesium bromide), n-propyl Grignard reagent (such as n-propyl magnesium chloride and n-propyl magnesium bromide), and i-propyl Grignard reagent (such as i-propyl magnesium chloride and i-propyl magnesium bromide). Of these examples, a favorable one is i-propyl Grignard reagent.
In the acetylene compound represented by the formula (4) above, R3 and R4 denote mutually independently a hydrogen atom, C1-20 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, di-C1-6-alkylaminocarbonyl group, phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, or di-C1-6-alkylaminocarbonyl group), furyl group, amino group, SiR7R8R9 (where R7, R8, and R9 are defined as above), or SnR10R11R12 (where R10R11, and R12 are defined as above).
The C1-20 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, di-C1-6-alkylaminocarbonyl group, SiR7R8R9 group, and SnR10R11R12 group are the same as those defined in the acetylene compound represented by the formula (1) above.
In the compound represented by the formula (5) above, R5 denotes a hydrogen atom, C1-20 alkyl group, or phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, or di-C1-6-alkylaminocarbonyl group); Z denotes CRxe2x80x2 (where Rxe2x80x2 denotes a hydrogen atom or C1-20 alkyl group) or a nitrogen atom; X6 denotes a halogen atom, C1-6 alkoxy group {which may be substituted with a phenyl group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group) or naphthyl group}, phenoxy group (which may be substituted with a C1-6 alkyl group, C1-6 alkoxy group, or phenyl group), naphthoxy group, SOnR6 group {where R6 denotes a C1-6 alkyl group or phenyl group (which may be substituted with a halogen atom or C1-6 alkyl group) and n denotes 1 or 2}, OSnR6 group (where R6 is defined as above), or OP(O)(OR13)2 group (where R13 denotes a C1-6 alkyl group); and m denotes 0 or 1.
The SOnR6 group is not specifically restricted; it includes, for example, methanesulfinyl, p-toluenesulfinyl, p-trifluoromethanesulfinyl, methanesulfonyl, benzenesuflonyl, p-toluenesulfonyl, and p-trifluoromethanesulfonyl. Of these examples, favorable ones are p-toluenesulfonyl and p-toluenesulfinyl.
The OSO2R6 group is not specifically restricted; it includes, for example, methanesulfonyloxy, benzenesufonyloxy, p-toluenesulfonyloxy, and p-trifluoromethanesulfonyloxy groups. Of these examples, a favorable one is p-toluene-sulfonyloxy group.
The OP(O)(OR13)2 group is not specifically restricted; it includes, for example, dimethyl phosphate, diethyl phosphate, and diphenyl phosphate. Of these example, a favorable one is diethyl phosphate.
Incidentally, the C1-20 alkyl group, phenyl group, C1-6 alkoxycarbonyl group, C1-6 alkylaminocarbonyl group, di-C1-6-alkylaminocarbonyl group, halogen atom, C1-6 alkoxy group, phenoxy group, and naphthoxy group are the same as those defined above.
In the diyne compound in the formula (8) above, the terminal substituent groups R1 and R4 are also defined as above.
Y denotes Z1-Z2-Z3 or Z4-Z5-Z6-Z7 {where Z1, Z3, Z4, Z5, and Z7 denote mutually independently Cxe2x95x90O or CR14R15  less than where R14 and R15 denote mutually independently a hydrogen atom or C1-6 alkyl group (which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 are defined as above)) greater than , Z2 and Z6 denote mutually independently O, S, Cxe2x95x90O, NR16  less than where R16 denotes a C1-6 alkyl group (which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 are defined as above)) greater than , or CR14xe2x80x2R15xe2x80x2  less than where R14xe2x80x2 and R15xe2x80x2 denote mutually independently a hydrogen atom, C1-6 alkyl group (which may be substituted with a C1-6 alkoxy group (which may be substituted with a phenyl group) or OSiR7R8R9 (where R7, R8, and R9 are defined as above)) greater than }.
Y is not specifically restricted; it includes, for example, (CH2)3,(CH2)4, CH2C(CH2OCH2Ph)2CH2, CH2C(CH2OSiMe3)2CH2, CH2C(CH2OSit-BuMe2)2CH2, CH2C(CH2OCH3)2CH2, CH2OCH2, CH2SCH2, CH2C(O)CH2, C(O)N(CH2Ph)CH2, C(O)N(CH3)CH2, C(O)N(CH2Ph)C(O), and C(O)N(CH3)C(O). Of these examples, favorable ones are (CH2)3, CH2C(CH2OCH2Ph)2CH2, and C(O)N(CH2Ph)CH2. Me stands for a methyl group, Ph stands for a phenyl group, and t-Bu stands for a t-butyl group.
In the compound represented by the formula (11) or (13), R3, R5, Rxe2x80x2, and X6 are defined as above. Yxe2x80x2 is the same as Y mentioned above.
A mention is given below of the process for producing the organotitanium compound represented by the formula (6) and/or (7).
The process consists of reacting an acetylene compound represented by the formula (1) in the presence of a titanium compound represented by the formula (2) and a Grignard reagent represented by the formula (3) with a compound represented by the formula (4) and further reacting with a compound represented by the formula (5), thereby giving the titanium compound represented by the formula (6) and/or (7) above.
The molar amount of the titanium compound used in this reaction should be 0.01-5 times, preferably 0.5-2 times, the amount of the acetylene compound (as the substrate) represented by the formula (1). The molar amount of the Grignard reagent should be 1-10 times the amount of the titanium compound used. The amount should be limited to 1.5-2.5 times in order to avoid side reactions with the substrate.
The reaction may be carried out by adding the reactants in any order. One procedure involves mixing the titanium compound and the Grignard reagent and then adding to the mixture the acetylene compound (as the substrate) represented by the formula (1). Another procedure involves adding the titanium compound to the acetylene compound represented by the formula (1), and then adding the Grignard reagent. Either procedure will do.
The molar amount of the compound represented by the formula (4) should be 0.5-2 times, preferably 0.6-1.2 times, the amount of the acetylene compound represented by the formula (1).
The molar amount of the compound represented by the formula (5) should be 0.5-2 times, preferably 0.8-1.5 times, the amount of the acetylene compound represented by the formula (1).
The solvent used in the reaction is not specifically restricted so long as it is not involved in the reaction. It includes, for example, aromatic hydrocarbons (such as benzene, toluene, xylene, mesitylene, chlorobenzene, and o-dichlorobenzene), aliphatic hydrocarbons (such as n-hexane, cyclohexane, n-octane, and n-decane), halogenated hydrocarbons (such as dichloromethane, dichloroethane, chloroform, and carbon tetrachloride), and ethers (such as tetrahydrofuran, diethyl ether, t-butyl methyl ether, and dimethoxyethane). Of these examples, favorable ones are dichloromethane, tetrahydrofuran, and diethyl ether. They may be used alone or in combination with one another.
The reaction temperature is not specifically restricted; it may range from xe2x88x92100xc2x0 C. to the boiling point of the solvent. Preferred reaction temperatures are within the range from xe2x88x9280xc2x0 C. to 40xc2x0 C. The reaction time is usually 0.1 to 1000 hours.
The above-mentioned reaction gives rise to the organotitanium compound represented by the above-mentioned formula (6) and/or (7). This compound is unstable out of the reaction system. Therefore, it is not isolated as such. Instead, the reaction system is given an electrophilic reagent to bring about addition reaction at the titanium bonding position, and the resulting addition product is isolated afterwards.
After the reaction is complete, the reaction system is given an aqueous solution of alkali to produce an aromatic compound in which a hydrogen atom is added to the titanium bonding position. Subsequently, this aromatic compound is extracted with an adequate solvent, and there is obtained a crude product upon condensation under reduced pressure. If necessary, the crude product is purified in the usual way by distillation, recrystallization, silica gel column chromatography, or the like. In this way it is possible to isolate the addition product in pure form.
It is presumed that the organotitanium compound represented by the formula (6) or (7) is formed by the following reaction mechanism.
The titanium compound and the Grignard reagent give rise to a divalent titanium complex, which reacts with the first acetylene compound represented by the formula (1) to give a titanacyclopropene intermediate. This intermediate reacts with the second acetylene compound represented by the formula (4) to give a titanacyclopendadiene intermediate. Between this intermediate and the compound represented by the formula (5) occurs cyclic addition reaction. This addition reaction eliminates the leaving group, thereby giving rise to the organotitanium compound represented by the formula (6) or (7).
It is presumed that the ratio in which the above-mentioned organotitanium compound is formed (or the orientation of the cyclic addition reaction) varies depending mainly on the electron-attracting property of the substituent group at the 1- and 4-position of the cyclopentadiene intermediate. 
A mention is made below of the process for producing the organotitanium compound represented by the formulas (9) and/or (10) above.
The diyne compound represented by the formula (8) is reacted with the compound represented by the formula (4) above in the presence of the titanium compound represented by the formula (2) above and the Grignard reagent represented by the formula (3) above. The resulting reaction product is further reacted with the compound represented by the formula (5) to give the organotitanium compound represented by the formulas (9) and/or (10) above.
The molar amount of the titanium compound used in this reaction is 0.01-5 times, preferably 0.5-2 times, the amount of the diyne compound (as the substrate) represented by the formula (8). The molar amount of the Grignard reagent should be 1-10 times the amount of the titanium compound used. The amount should be limited to 1.5-2.5 times in order to avoid side reactions with the substrate.
The reaction may be carried out by adding the reactants in any order. One procedure involves mixing the titanium compound and the Grignard reagent and then adding to the mixture the diyne compound (as the substrate) represented by the formula (8). Another procedure involves adding the titanium compound to the diyne compound represented by the formula (8), and then adding the Grignard reagent. Either procedure will do.
The molar amount of the compound represented by the formula (5) should be 0.5-2 times, preferably 0.8-1.5 times, the amount of the diyne compound represented by the formula (8).
The solvent used in the reaction is not specifically restricted so long as it is not involved in the reaction. It includes those which have been listed above.
The reaction temperature is not specifically restricted; it may range from xe2x88x92100xc2x0 C. to the boiling point of the solvent. Preferred reaction temperatures are within the range from xe2x88x9280xc2x0 C. to 40xc2x0 C. The reaction time is usually 0.1 to 1000 hours.
The above-mentioned reaction gives rise to the organotitanium compound represented by the above-mentioned formula (9) and/or (10). This compound is unstable out of the reaction system. Therefore, it is not isolated as such. Instead, the reaction system is given an electrophilic reagent to bring about addition reaction at the titanium bonding position, and the resulting addition product is isolated afterwards.
It is presumed that the organotitanium compound represented by the formula (9) or (10) is formed by the following reaction mechanism. The reaction mechanism is identical with that mentioned above, except that two molecules of the acetylene compounds represented by the formulas (1) and (4) are replaced by the diyne compound represented by the formula (8). 
A mention is made below of the process for producing the organotitanium compound represented by the formulas (12) above.
The diyne compound represented by the formula (11) is reacted with the acetylene compound represented by the formula (1) above in the presence of the titanium compound represented by the formula (2) above and the Grignard reagent represented by the formula (3) above. In this way it is possible to produce the organotitanium compound represented by the formula (12) above.
The molar amount of the titanium compound used in this reaction is 0.01-5 times, preferably 0.5-2 times, the amount of the acetylene compound (as the substrate) represented by the formula (1). The molar amount of the Grignard reagent should be 1-10 times the amount of the titanium compound used. The amount should be limited to 1.5-2.5 times in order to avoid side reactions with the substrate.
The reaction may be carried out by adding the reactants in any order. One procedure involves mixing the titanium compound and the Grignard reagent and then adding to the mixture the acetylene compound (as the substrate) represented by the formula (1). Another procedure involves adding the titanium compound to the acetylene compound represented by the formula (1), and then adding the Grignard reagent. Either procedure will do.
The molar amount of the diyne compound represented by the formula (11) is 0.5-2 times, preferably 0.8-1.5 times, the amount of the acetylene compound represented by the formula (1).
The solvent used in the reaction is not specifically restricted so long as it is not involved in the reaction. It includes those which have been listed above.
The reaction temperature is not specifically restricted; it may range from xe2x88x92100xc2x0 C. to the boiling point of the solvent. Preferred reaction temperatures are within the range from xe2x88x9280xc2x0 C. to 40xc2x0 C. The reaction time is usually 0.1 to 1000 hours.
The above-mentioned reaction gives rise to the organotitanium compound represented by the above-mentioned formula (12). This compound is unstable out of the reaction system. Therefore, it is not isolated as such. Instead, the reaction system is given an electrophilic reagent to bring about addition reaction at the titanium bonding position, and the resulting addition product is isolated afterwards.
It is presumed that the organotitanium compound represented by the formula (12) is formed by the following reaction mechanism. The reaction mechanism is identical with that mentioned above, except that two molecules of the acetylene compounds represented by the formulas (4) and (5) are replaced by the diyne compound represented by the formula (11). The reaction product has such a structure that the titanacyclopentadiene intermediate is connected to the acetylene compound as the third component. This determines the orientation of the cyclic addition and gives rise to a single organotitanium compound. 
A mention is made below of the process for producing the organotitanium compound represented by the formulas (14) above.
The acetylene compound represented by the formula (1) is reacted with two molecules of the acetylene compound represented by the formula (13) above in the presence of the titanium compound represented by the formula (2) above and the Grignard reagent represented by the formula (3) above. In this way it is possible to produce the organotitanium compound represented by the formula (14) above.
The molar amount of the titanium compound used in this reaction is 0.01-5 times, preferably 0.5-2 times, the amount of the acetylene compound (as the substrate) represented by the formula (1). The molar amount of the Grignard reagent should be 1-10 times the amount of the titanium compound used. The amount should be limited to 1.5-2.5 times in order to avoid side reactions with the substrate.
The reaction may be carried out by adding the reactants in any order. One procedure involves mixing the titanium compound and the Grignard reagent and then adding to the mixture the acetylene compound (as the substrate) represented by the formula (1). Another procedure involves adding the titanium compound to the acetylene compound represented by the formula (1), and then adding the Grignard reagent. Either procedure will do.
The molar amount of the acetylene compound represented by the formula (13) is 1-4 times, preferably 1.6-3 times, the amount of the acetylene compound represented by the formula (1).
The solvent used in the reaction is not specifically restricted so long as it is not involved in the reaction. It includes those which have been listed above.
The reaction temperature is not specifically restricted; it may range from xe2x88x92100xc2x0 C. to the boiling point of the solvent. Preferred reaction temperatures are within the range from xe2x88x9280xc2x0 C. to 40xc2x0 C. The reaction time is usually 0.1 to 1000 hours.
The above-mentioned reaction gives rise to the organotitanium compound represented by the above-mentioned formula (14). This compound is unstable out of the reaction system. Therefore, it is not isolated as such. Instead, the reaction system is given an electrophilic reagent to bring about addition reaction at the titanium bonding position, and the resulting addition product is isolated afterwards.
It is presumed that the organotitanium compound represented by the formula (14) is formed by the following reaction mechanism.
The titanium compound and the Grignard reagent give rise to a divalent titanium complex, which reacts with two molecules of the compounds having a triple bond to give a titanacyclopentadiene intermediate. This intermediate reacts with one molecule of the compound represented by the formula (13) for cyclic addition reaction. This addition reaction brings about transfer of titanium-carbon bond and eliminates the leaving group, thereby giving rise to the organotitanium compound represented by the formula (14). 
(B) Process for Addition Reaction
According to the present invention, the process for addition reaction consists of adding to the organotitanium compound obtained by the above-mentioned process a compound having an electrophilic functional group or an electrophilic reagent, and performing addition reaction on the organotitanium compound.
The electrophilic functional group is not specifically restricted so long as it reacts with the organotitanium compound of the present invention. It is preferably aldehyde group, ketone group, imino group, hydrazone group, aliphatic double bond, aliphatic triple bond, acyl group, ester group, or carbonate group. The compound having an electrophilic functional group includes, for example, aldehyde compound, ketone compound, imine compound, hydrazone compound, olefin compound, acetylene compound, acyl compound, ester compound, xcex1,xcex2-unsaturated carbonyl compound, and carbonate ester compound.
The aldehyde compound is not specifically restricted. It includes, for example, C1-10 alkyl aldehyde, C4-6 cycloalkyl aldehyde, C3-14 cycloalkenyl aldehyde, benzaldehyde, o-halogenobenzaldehyde, m-halogenobenzaldehyde, p-halogeno-benzaldehyde, C1-10 alkyl ester-substituted phenyl aldehyde, o-halogenosuccin aldehyde, m-halogenosuccin aldehyde, p-halogenosuccin aldehyde, furylaldehyde, and thiophen aldehyde.
The ketone compound includes, for example, C3-20 alkyl ketone, C4-30 alkyl ester-substituted alkyl ketone, C3-10 cycloalkyl ketone, acetophenone, tetralone, decalone, furyl ketone, and thiophenoketone. The imine compound includes, for example, the reaction product of the above-mentioned aldehyde compound with C1-10 alkylamine, aniline, or benzylamine.
The hydrazone compound includes, for example, the reaction product of the above-mentioned ketone compound with C1-10 alkyl hydrazine.
The olefin compound includes, for example, allyl alcohol derivatives which may have a substituent group. The allyl alcohol derivative includes, for example, C4-13 allyl alcohol alkyl ester and C4-13 allyl alcohol alkyl carbamate.
The allyl alcohol derivative may have a substituent group such as C1-20 alkyl group, phenyl group, o-halogeno-phenyl group, m-halogenophenyl group, and p-halogenophenyl group.
The acetylene compound includes, for example, propargyl alcohol derivative which may have a substituent group and propargyl halide which may have a substituent group. The propargyl alcohol derivative includes, for example, C4-13 propargyl alcohol alkyl ester, C4-13 propargyl alcohol alkyl carbamate, C4-13 propargyl alcohol alkyl ether, C4-13 propargyl alcohol alkylsulfonic ester, propargyl alcohol-o-hydroxyphenylsulfonic ester, propargyl alcohol-m-hydroxyphenylsulfonic ester, propargyl alcohol-p-hydroxy-phenylsulfonic ester, and C4-13 propargyl alcohol alkyl phosphoric ester.
The propargyl halide includes, for example, propargyl chloride and propargyl bromide.
These propargyl alcohol derivatives and propargyl halides may have a substituent group such as C1-20 alkyl group, phenyl group, o-halogenophenyl group, m-halogenophenyl group, p-halogenophenyl group, and trialkylsilyl group.
The electrophilic reagent is not specifically restricted so long as it reacts with the organotitanium compound of the present invention. It is preferably water, heavy water, chlorine, bromine, iodine, N-bromosuccinimide, oxygen, carbon dioxide gas, or carbon monoxide.
To be concrete, the process consists of adding to the organotitanium compound (prepared as mentioned above) the compound having an electrophilic functional group or the electrophilic reagent (which are collectively referred to as an electrophilic compound hereinafter), thereby causing addition reaction with the electrophilic compound to take place at the titanium bonding position.
The molar amount of the electrophilic compound should be 1-10 times, preferably 1-5 times, particularly 1-2 times, the amount of the organotitanium compound.
The reaction may be carried out by adding the electrophilic compound in any order. One procedure involves adding the electrophilic compound directly to the reaction system in which the organotitanium compound has been prepared. Another procedure involves adding a solution of the organotitanium compound to a solution in which the electrophilic compound has been dissolved. Either procedure will do.
The solvent used in the reaction is not specifically restricted so long as it is not involved in the reaction. It includes those which have been used for the production of the organotitanium compound.
The reaction temperature is not specifically restricted; it may range from xe2x88x92100xc2x0 C. to the boiling point of the solvent. Preferred reaction temperatures are within the range from xe2x88x9280xc2x0 C. to 40xc2x0 C. The reaction time is usually 0.1 to 1000 hours.
After the reaction is complete, the addition reaction product is extracted with an adequate solvent, and there is obtained a crude product upon condensation under reduced pressure. If necessary, the crude product is purified in the usual way by distillation, recrystallization, silica gel column chromatography, or the like. In this way it is possible to isolate the desired product in pure form.